Local chemotherapy in the rat brainstem with multiple catheters: a feasibility study

Objects  Technical aspects of local chemotherapy in inoperable brainstem gliomas by convection-enhanced delivery (CED) are still under experimental considerations. In this study, we characterize the feasibility of multiple cannula placements in the rat brainstem. Materials and methods  In 38 male Fisher rats, up to three guided screws were positioned in burr holes paramedian at 2.5 mm anterior and posterior to as well as at the lambdoid suture. Using Alzet™ pumps (1 μl/h flow rate over 7 days) either vehicle (5% dextrose) or 0.1 mg carboplatin was delivered via one, two, or three cannulas, respectively. During cannula insertion, electrocardiogram and respiratory rate was monitored. All rats were subsequently evaluated neurologically for 8 days. For drug distribution in coronal sections, the brain tissue concentration of platinum was measured. HE staining was used to evaluate the local site of drug delivery. Heart and respiratory rate remained within normal range during surgical procedure. Neurological scoring showed only mild neurological impairment in the groups receiving two or three cannulas, which resolved after vehicle delivery. However, after carboplatin delivery, this deficit remained unchanged. Drug distribution was more homogeneous in the three cannula group. Histological slices visualized edematous changes at the sight of cannula placement. Conclusion  The unilateral application of up to three cannulas in the brainstem of rats for local drug delivery studies is feasible. The remaining neurological deficit in carboplatin-treated animals underlines the need of low toxicity drugs for CED in the brainstem.     

An experimental brainstem tumor model using in vivo bioluminescence imaging in rat

Purpose  Currently, there is no conclusive treatment for brainstem tumor. To facilitate the development of new treatments, it is essential to establish predictive preclinical in vivo models in which therapeutic modalities can be evaluated. Although a few rodent models have been reported, there is no novel approach that can monitor tumor response qualitatively and quantitatively. Materials and methods  Bioluminescence imaging was used to characterize a rat brainstem tumor model. In this model, 9L gliosarcoma cells, transduced with an onco-retroviral vector containing the luciferase coding sequence, were inoculated into Fisher 344 rats. Result  Histopathological assessment showed successful cell implantation into the brainstem. There was a strong correlation between pathological tumor volume and luminescence strength. Longitudinal quantitative responses of the tumor after application of a therapeutic agent were also demonstrated. Conclusion  This study demonstrates a robust rodent model with the ability to monitor brainstem tumor growth and response to chemotherapeutic agents.     

大鼠脑干胶质瘤模型的建立及MRI特点

目的 建立大鼠脑干胶质瘤模型,并研究成瘤鼠运动功能及胶质瘤MRI成像特点.方法 采用大鼠脑立体定向仪,将C6胶质瘤细胞接种至SD大鼠脑干内.MRI动态观察肿瘤生长情况,并观察接种C6胶质瘤细胞后大鼠的运动能力、生存周期等.结果 C6胶质瘤细胞接种成功率为100%.生存分析表明:大鼠于接种后第16～22天死亡.接种后第7天,MRI即可检出肿瘤生长,荷瘤鼠的运动能力随着成瘤时间的推移逐渐减弱.结论 大鼠脑干胶质瘤模型成瘤率高,有良好的可重复性和可预测性.MRI观察该模型具有脑干胶质瘤成像的特点,细胞接种后10～18 d是最佳观测期.     

大鼠C6脑胶质瘤生长的动态观察和MR灌注成像可行性研究

目的研究大鼠C6脑胶质瘤的生长规律,初步探讨其MR灌注成像研究的可行性。方法立体定向技术将C6细胞接种在13只SD大鼠的右侧尾状核建立模型。MR增强扫描动态观察第一组8只大鼠的肿瘤生长状况。在瘤龄第17 d,对笫二组5只荷瘤大鼠进行磁共振灌注成像(MR PWI)检查,根据时间-信号曲线计算为相对脑血容量(rCBV)和最大信号下降百分比(SRRmax)值。结果第一组大鼠生存期为23.5±3.93 d。肿瘤最大径随瘤龄增长呈线性增大,体积呈指数规律增大,濒死前肿瘤的最大径为9.19±236 mm,体积为515.66±303.33 mm3。第二组大鼠皆成功进行了MR PWI检查,肿瘤组织和正常脑组织rCBV分别为179.04±46.02和87.04±23.00,SRRmax分别为39.91％±6.80％和24.11％±6.36％,肿瘤组织和正常脑组织有显著性差异(P<0.01)。结论大鼠C6脑胶质瘤肿瘤生长有规律性,可用作MR PWI研究。